Etiology and Severity of Acute Chest Syndrome in Sickle Cell Disease Pulmonary complications are the major cause of mortality and morbidity in Sickle Cell Disease. Since the etiology of most cases of Acute Chest Syndrome are not determine, there is an inability to establish a specific treatment regimen. Our hypothesis is that the variability in clinical course noted in children and adults can be explained by identifying the precipitating factors or etiology agents which lead to this complication. Furthermore, by identifying such factors we will be in a better position to design appropriate clinical interventions and minimize the morbidity and mortality associated with ACS. Our specific aims for this project are 1) to prospectively determine the type and incidence of infectious agents and non-infectious factors in patients with ACS and to characterize the clinical and laboratory findings associated with each course, and 2) to initiate a collaborative study which will use standard treatment protocols and is designed to collect data to characterize the clinical severity, histopathology and laboratory findings in ACS associated with each specific etiology. Preliminary data suggests that certain infectious (chlamydia, mycoplasma, viruses and bacteria) and non- infectious (fat embolism) causes of ACS are under-diagnosed and therefore, inadequately treated. The collaborative study will include at least 12 sickle cell programs who have agreed to follow standard guidelines. All cases will undergo extensive evaluation for an infectious etiology and be assessed for pulmonary fat embolism, pulmonary emboli and other non-infectious etiologies. The clinical course will be quantitatively assessed by a protocol including extensive pulmonary evaluation. In all cases where tissue is available (pre or post-mortem) analysis will be performed at a central sickle cell pathology resource. Statistical analysis of all information will be performed. We anticipate that the results of this study will provide a foundation for future clinical trials to evaluate specific therapeutic modalities in ACS.